HILDRETH LAB

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们以前的工作和其他人的工作清楚地表明了胆固醇在HIV复制中的重要作用。我们已经证明，胆固醇螯合剂β-环糊精作为HIV杀微生物剂具有重要的前景。胆固醇在HIV生物学中的重要性是基于这种脂质在膜生物学中的作用，包括生物膜的融合。在过去的一年里，我们已经获得证据表明胆固醇可能对HIV转录也有直接影响。我们的研究结果表明，一个转录因子，其表达与胆固醇合成相关的基因直接激活HIV基因转录共调节。这些结果表明，细胞和组织中的胆固醇水平可能会在基因转录水平上影响HIV复制。此外，这些结果对与使用抗逆转录病毒药物相关的脂肪代谢障碍具有重要意义，其中一些药物严重干扰脂质体内平衡。他汀类药物对HIV释放和HIV蛋白合成的矛盾作用也可以部分地由这一新的观察结果来解释。这些研究在细胞系和原代细胞中进行，证实了该观察结果在体内的潜在重要性。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our previous work and that of others clearly demonstrate the important role cholesterol plays in the replication of HIV. We have shown that a cholesterol-sequestering agent betacyclodextrin holds significant promise as an HIV microbicide. The importance of cholesterol in HIV biology to this point has been based on the role this lipid plays in membrane biology, including the fusion of biological membranes. Over the last year we have obtained evidence that cholesterol may have a direct effect on HIV transcription as well. Our results indicate that a transcription factor whose expression is co-regulated with that of genes related to cholesterol synthesis directly activates HIV gene transcription. These results indicate that cholesterol levels in cells and tissues may impact HIV replication at the level of gene transcription. Furthermore, the results have significant implications for lipodystrophy associated with the use of anti-retroviral drugs some of which profoundly disturb lipid homoestasis. The paradoxical effects of statins on HIV release and HIV protein synthesis may also be explained in part by this novel observation. These studies have been carried out in both cell lines and primary cells confirming the potential importance of this observation in vivo.